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Design, synthesis, biological evaluation and in silico studies of EGFR inhibitors based on 4-oxo-chromane scaffold targeting resistance in non-small cell lung cancer (NSCLC).
- Source :
- Medicinal Chemistry Research; Sep2022, Vol. 31 Issue 9, p1500-1516, 17p
- Publication Year :
- 2022
-
Abstract
- Allosteric kinase inhibitors targets kinases with oncogenic driver mutations in malignancies as a potential new therapy strategy. EGFR inhibitors with a 4-oxo-chromane scaffold targeting the L858R/T790M/C797S mutation were identified, optimized, synthesized, and assessed for anticancer and EGFR enzyme inhibitory activity. Compounds 4i and 4l were shown to be very effective with IC<subscript>50</subscript> values of 132 and 146 nM, respectively, and excellent selectivity in in silico study. Compound 4i showed substantial antioxidant activity at a concentration of 100 µM, with a DPPH radical scavenging value of 91.46%. The synthesized compounds 4i, 4k and 4l were found to be selective toward cancer cells since they did not exhibit cytotoxicity even at IC<subscript>50</subscript> > 20 µM on normal cells. Compound potency was further assessed using in silico and in vitro biological evaluation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10542523
- Volume :
- 31
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Medicinal Chemistry Research
- Publication Type :
- Academic Journal
- Accession number :
- 158445974
- Full Text :
- https://doi.org/10.1007/s00044-022-02929-4